A lectin domain exists in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A: GnT-IVa) C-terminal region

A group from Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Japan, etc. has discovered a lectin domain in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A: GnT-IVa) C-terminal region.

The biosynthesis of the GlcNAc branches existing in N-glycans is catalyzed by the specific N-acetylglucosaminyltransferases (GnTs), GnT-I to -V.

Authors have found that the lectin domain discovered in GnT-IVa forms a β-sandwich fold composed of nine β-strands with three short α-helices, and this domain shows structural and functional similarities with bacterial CBM32 acting as a lectin with a preference for GlcNAc.

It was also found that the lectin domain of GnT-IVa is required for the efficient N-glycan biosynthesis toward glycoprotein substrates in cells.

Glycan features defining cells differentially susceptible to HIV: Single-cell level study

A group from Department of Urology, University of California, San Francisco, USA, etc. has reported that HIV upregulates the levels of cell-surface fucose and sialic acid in a cell-intrinsic manner, and that memory CD4+ T cells co-expressing high levels of fucose and sialic acid are highly susceptible to HIV infection.

Glycans were remodeled on the surface of HIV-infected cells. Both total sialic acid (recognized by WGA, which also binds to N-acetylglucosamine) and α2–3 linked sialic acid (recognized by MAL-1) were upregulated by HIV during infection as shown below.

where, uninfected (UI), predicted precursor (PRE), and infected (INF) CD4+ cells.

In addition, it was confirmed that HIV preferentially infects memory CD4+ T cells from tonsils and PBMCs co-expressing high levels of fucose and sialic acid.

here, infectivity was assessed by HSA positivity.

Defucosylation promotes macroautophagy

A group from Tumour Cell Death and Autophagy Laboratory, Cancer Research UK Beatson Institute, Glasgow, UK, etc. has reported that glycan degradation promotes macroautophagy.

Since macroautophagy is a major mechanism for the degradation of long-lived proteins and the only mechanism to degrade organelles described so far, perturbation of autophagy can lead to a variety of diseases, including neurodegenerative diseases, inflammatory diseases, diabetes, and cancer.

Due to the large proportion of proteins that are glycosylated, it was postulated that macroautophagy must be dependent not only on enzymes that degrade polypeptides, but also on those that degrade glycans.

Authors have found that glycan breakdown, specifically defucosylation, is a contributing step in the process of macroautophagy.
It was shown that loss of expression of the lysosomal glycosidase FUCA1 in cells and tissues causes accumulation of autophagosomes, indicating that FUCA1 modulates both basal and stimulated autophagy. Furthermore, it was shown that FUCA1 supports both autophagosome–lysosome fusion (loss of FUCA1 causes a stall in the fusion process) and the turnover stage of autophagy (loss of FUCA1 caused an increase in LC3-II levels under baseline conditions, but do not completely block, the turnover stage of the process). It is notable that under starvation conditions, it was found that FUCA1 loss decreases the rate of autophagosome clearance, as well as the degradation of mitochondria upon induction of mitophagy, indicating that FUCA1 is required for efficient autophagic flux in multiple contexts.

The importance of FUCA1 is exemplified by mutations in the gene, which lead to the congenital lysosomal storage disorder fucosidosis.

Biofilm forming rhizobacteria isolated from the rhizospheres of native arid grassland plants

A group from Department of Soil Science, University of Maragheh, Maragheh, Iran, etc. has reported about effects of biofilm forming rhizobacteria isolated from the rhizospheres of native arid grassland plants onto wheat growth.

Water deficit is expected to cause serious problems for crops on more than 50% of the earth’s arable lands by 2050. With ongoing global climate change the severity, frequency and duration of drought periods are predicted to further increase. Thus, understanding and improving plant survival as well as growth under restricted water availability is of central significance in contemporary plant science and consequently is a prerequisite for efficient plant production.

The principal idea of this study was to isolate bacteria that promote plant growth under drought stress, support plant nutrition by solubilizing nutrients, promoting plant growth and form biofilms. In order to obtain a diverse collection of root-associated and drought-tolerant bacteria, the bacteria were isolated from roots of five grass species (Gramineae) grown in natural grassland systems on low moisture soils of East Azerbaijan, Iran. Subsequently, the growth promoting abilities of the isolated strains were tested on two wheat cultivars in a pot experiment.

at three levels of water availability and without (B0) or with the rhizobacteria strain 16-1 (B1), strain 38-2 (B2) and, strain 54-1 (B3).

By isolating bacteria from grass rhizospheres in an arid ecosystem and filtering during the collection process for biofilm-forming bacteria with multiple plant growth promoting properties, authors obtained three promising candidate strains for yield improvement of wheat. As expected, the positive influences of these bacteria were evident under moderate and/or severe water stress, suggesting that the hot and dry climate of East Azerbaijan grasslands promotes the evolution of drought tolerant Plant Growth Promoting Bacteria.

Galectin-4 and Obesity

A group from Department of Clinical Sciences, Lund University, Jan Waldenströms gata 15, floor 5, Malmö, Sweden, etc. has reported about interesting correlation between Galectin-4 and a type of Obesity.

Obesity (BMI ≥30 kg/m2) contributes to health complications and reduces life expectancy with up to approximately 20 years. This is mainly due to the significantly increased risk of developing numerous non-communicable diseases, such as type 2 diabetes (DM2), cardiovascular disease (CVD) and certain types of cancer.

Gal-4 is expressed almost exclusively in the gastrointestinal tract of healthy individuals, where it plays a role in controlling intestinal inflammation. It reduces proinflammatory cytokine production in the intestinal mucosa, and knockdown of the Gal-4 peptide promotes colorectal cancerogenesis. This suggests that Gal-4 plays a significant role in the pathophysiology of the development of both inflammatory bowel disease and colorectal cancers. However, the physiological role of Gal-4 is multifaceted and further include apical protein trafficking, lipid raft stabilization, intestinal wound healing and bacterial pathogen fighting. Epidemiological data also strongly propose an involvement of Gal-4 in cardiometabolic diseases, suggesting it may be considered as a predictive biomarker for the development of CVD and diabetes.

In this study, comparing hospitalized subjects with obesity (HO) with non-hospitalized subjects with obesity (NHO), it was found that the Gal-4 level was associated with a higher probability of being HO in the fully adjusted logistic regression model (OR 1.72; CI95% 1.16–2.54; p = 0.007).

Very curious, isn’t it?

Silencing Galactin-1 could be effective in suppressing Glioblastoma

A group from Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL USA, etc. has reported that Galectin-1 activates carbonic anhydrase IX and modulates glioma metabolism.

Galectin 1 (Gal-1) and Galectin 3 (Gal-3) have been studied in relation to Glioblastoma (GBM). Gal-1 binds intact β-galactose molecules on the cell surface and extracellular matrix. Accumulating evidence shows that Gal-1 plays an important role in cancer (colon, breast, lung, head and neck, prostate cancer, and GBM) since its expression correlates with tumor aggressiveness such as proliferation, invasion and progression.

This report highlights that Gal-1 plays an important role in GBM Stem Cell (GSC) metabolism through mechanisms mediated by carbonic anhydrase IX (CA-IX), the surrogate marker of hypoxia. Gal-1 is under the transcriptional control of HIF-1α, and in turn, Gal-1 exerts its metabolic influence via physical association with CA-IX. Silencing Gal-1 reverses the Warburg effect by reducing the expression of CA-IX. Thus, targeting the Gal-1/CA-IX signaling pathway provides a new strategy for reversing the Warburg effect in GBM and inhibiting the progression of GSC-induced cancer growth.

where, GAPHD: Glyceraldehyde 3-phosphate dehydrogenase; NPC: neural progenitor cells

Silencing Gal-1 made to live longer in mice models.

What promotor is required in root colonization of Arbuscular mycorrhiza fungi (AMF)

A group from CUHK Shenzhen Research Institute, No. 10 Yuexing 2nd Road, Nanshan, Shenzhen, China, has reported that rice Phosphate Response Regulator 2 (PHR2) is required for root colonization by AM fungi (AMF). Root colonization of PHR2 mutants is drastically reduced at low Phosphate (Pi), while ectopic PHR2 expression partially rescues root colonization at high Pi.

When plants obtain sufficient phosphate, SPX (SYG1/PHO81/XPR1) proteins prevent nuclear translocation of PHR2, as well as PHR2 binding to promoters of phosphate starvation -induced genes including AM relevant genes. This causes low exudation of strigolactone and poor expression of genes required for perception of Myc-Factors and fungal entry, thereby preventing full symbiosis development.

Upon phosphate starvation, SPX proteins, are degraded. Consequently, PHR2 is active, can bind to P1BS elements in promoters, and transcriptionally activate genes important for AM, such as CCD7 involved in strigolactone biosynthesis for activation of the fungus in the rhizosphere prior to contact, genes encoding receptors involved in the perception of fungal signals prior to root contact such as CERK1 which is necessary for the establishment of the mycorrhizal interaction as well as for resistance to the rice blast fungus, and SYMRK which is required for both fungal and bacterial recognition, the transcription factor NSP2, ZAS involved in apocarotenoid biosynthesis promoting root colonization, and the AM-specific phosphate transporter gene PT11 (localized to the peri-arbuscular membrane) required for Pi uptake from the fungus. Consequently, at low phosphate, roots exude increased amounts of strigolactone and can perceive fungal signals, the fungus is activated to colonize the roots and the symbiosis can function through nutrient transporters localizing to the peri-arbuscular membrane. Thus, symbiosis establishment appears to be enabled as a result of the PHR2-regulated phosphate starvation response.

Arb.: Arbuscules; Ves.: Vesicles; phr2(C): CRISPR-Cas9 generated phr2 mutant

No difference in disease severity between omicron lineages BA.4/BA.5 and BA.1

A group from Health Intelligence, Western Cape Government: Health and Wellness, South Africa, etc. has reported about disease severity of omicron lineages BA.4/BA.5.

Among 3,793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had lower risk of severe outcomes than previous waves (Ancestral, beta, and delta).

Rice Rhizosphere: Arthrobacter sp. GN70 could be the best PGPR

A group from Department of Life Science, Dongguk University-Seoul, Goyang 10326, Korea has reported that Arthrobacter sp. GN70 inoculated into the rice plants showed a significantly positive effect on shoot length, root length, fresh plant weight, and dry plant weight.

In this study, 504 strains were isolated through culture-dependent methods and tested for the PGPB traits for each strain. Based on its high IAA value, PGPB traits, and antagonism towards pathogenic microorganisms, Arthrobacter sp. GN70 was selected for inoculation in rice plants, under lab and greenhouse conditions. Strain GN70 successfully attached to the roots, produced fibril matrix, and enhanced the rice plant growth, lateral roots, and weight. The strain also showed antagonistic effects towards plant and human pathogens.

The Arthrobacter species, designated as GN70, produced the highest amount of IAA (50.3 µg/mL) among other PGPB including Sphingomonas, Ideonella, Burkholderia, and Agromyces.
The colonization of the rice root surface by Arthrobacter sp. GN70 was significant as shown below.

(a) Arthrobactor sp. colonized, (b) control

Arthrobacter sp. GN70 produces EPS, which may hold water or increase the water-holding capacity in the soil to assist the bacteria and the plant roots under water-deficit stress. The ability to form biofilms both enhances bacterial survival and also enhances plant growth through the various PGPR-associated mechanisms. The GN70 can be utilized as plant growth promoters, suppressors of plant pathogens, and alleviators of water-deficit stress. Actually, the antifungal activity of GN70 showed an inhibitory region in the F. proliferatum KACC 44025, which mainly affects the rice plant with rice spikelet rot disease.

Based on the t-test, the rice seeds inoculated with Arthrobacter sp. GN70 increased significantly in shoot length, root length, fresh plant weight, and dry plant weight by 143.5%, 83.5%, 112.1%, and 256.7%, respectively.

Innate immune lectin galectin-7 (Gal-7) binds a variety of distinct microbes and kills

A group from Joint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA, etc. has reported that the innate immune lectin galectin-7 (Gal-7) binds a variety of distinct microbes, all of which share features of blood group-like antigens.
<a href=”https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218387/”>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218387/</a>

It has been known that several members of the galectin family, including galectin-3 (Gal-3), galectin-4 (Gal-4), and galectin-8 (Gal-8), possess the ability to bind blood group A and B with high affinity. Although prior studies demonstrated that Gal-3, Gal-4, and Gal-8 are capable of binding and killing microbes that utilize blood group-like molecular mimicry, the extent to which other members of the galectin family likewise share the ability to provide innate immunity against molecular mimicry remains incompletely defined.

In this report, it was demonstrated that Gal-7 also possesses the ability to bind and kill microbes that utilize blood group molecular mimicry. However, unlike Gal-3, Gal-4, and Gal-8, Gal-7 exhibits very little affinity for mammalian A and B antigens. Despite this, Gal-7 exhibited high specificity toward multiple microbes that express glycans with blood group-like features. These results demonstrate that antimicrobial activity among galectin family members is not limited to Gal-3, Gal-4, and Gal-8, but that Gal-7 likewise possesses the ability to bind and kill microbes expressing blood group-like antigens.

From microarray studies using CFG glycan arrays, at 0.04 μM, Gal-7 engaged only three glycan structures out of nearly 600, a <strong>type 2 (Galβ1-4GlcNAc) blood group A</strong> structure, and two <strong>polylactosamine (polyLacNAc, i blood group)</strong> containing structures capped with the H antigen. At 3.3 μM Gal-7 exhibited binding toward additional glycans, including several glycans containing the blood group B antigen. At 10 μM, Gal-7 is bound to a common non-blood group containing glycans recognized by other galectin family members, including biantennary N-glycans and those with poly-N-acetyllactosamine (polyLacNAc) structures. The selective binding specificity of Gal-7 over a broad range of concentrations distinguishes it from prior reports on other galectins and suggests that unlike Gal-3, Gal-4, and Gal-8, Gal-7 may not readily engage blood group positive microbes.

Although the mechanism whereby Gal-7 and other galectins kill microbes is unclear, the results of this study suggest that an ancient carbohydrate binding protein family expressed in mammals exists that can target a variety of microbes, each of which utilize features of blood-group molecular mimicry.